OBJECTIVE: To review the safety and efficacy of alternative intermittent statin dosing regimens in patients with previous intolerance due to myopathy. DATA SOURCES: Literature was accessed through MEDLINE (1946 -December 2012) and EMBASE (1966-December 2012) using relevant MeSH and Emtree search terms, including statins, HMG Co-A reductase inhibitors, simvastatin, atorvastatin, lovastatin, fluvastatin, pravastatin, pitavastatin, rosuvastatin, myopathy, and myalgias. Web of Science (1955-December 2012) and the aforementioned databases were additionally searched using combinations of the following text words: statin intolerance, alternate dosing, nondaily dosing, weekly dosing, statin-induced myopathy, and intermittent statin dosing. References of identified articles were reviewed for additional citations. STUDY SELECTION AND DATA EXTRACTION: All identified English-language peer-reviewed publications were evaluated. Articles (excluding meeting abstracts) specifically addressing nondaily statin use in patients with previous statin-induced myopathy were reviewed. DATA SYNTHESIS: Although statins have achieved significant reductions in cardiovascular morbidity and mortality, as many as 10% of patients prescribed these therapies experience myopathies. Intermittent statin regimens ranging from every-other-day to once-weekly dosing have emerged in an attempt to maintain efficacy while moderating the incidence of adverse effects. The results reported in 10 publications investigating varying regimens with atorvastatin and/or rosuvastatin revealed that at least 70% of patients were able to tolerate an intermittent dosing strategy without a recurrence of previous treatment-limiting adverse effects. Although the degree of low-density lipoprotein cholesterol-lowering varied appreciably among studies (12-38%), the addition of a nondaily statin regimen facilitated attainment of National Cholesterol Education Program goals for some. CONCLUSIONS: Although areas of uncertainty remain, intermittent dosing (particularly with rosuvastatin and atorvastatin) in previously intolerant patients is a useful strategy to capitalize on the benefits of this therapy. Larger scale randomized trials are necessary to more clearly define the role of this strategy and the optimal choice of regimen.